Thursday September 6, 2018 • TMEC L-007, 2pm

I. First class organizational meeting and course introduction • Drummond

II. Lecture:

Germ cells: resetting pluripotency • Kamei

Germ cells are essential for species propagation, by providing both genetic continuity and the opportunity for genetic reshuffling among generations. In most organisms, cells of the germ lineage undergo ordered differentiation events to yield highly specialized cells (eggs or sperm) with defined functions (fertilization), but which retain the capacity to return to totipotency following fertilization. This discussion will focus on genetic and epigenetic mechanisms by which germ cells achieve this remarkable balance between specialized differentiation and totipotency. Germ_Cell_Lecture.ppt

Review Article: sasaki_matsui_germ_review.pdf GermCellDev.pdf tang surani human PGC review.pdf

Friday September 7, 2018

BBS Student Retreat - No Class

All remaining classes: Fridays 2 - 5 PM, MGH Simches Research Building, Room 3.120, 185 Cambridge Street

MGH Class Location and Shuttle Bus

Friday September 14, 2018 • Simches 3.120

I. Paper discussion: Germ Cells: hikabe hayashi female germline.pdf hikabe hayashi female germline supp.pdf

II. Lecture:

Genomic Equivalence and pluripotency • Hochedlinger

Where did our current ideas about pluripotency and cell reprogramming arise? What are pluripotent cells? How can we find factors that regulate pluripotency? What is the difference between an embryonic stem cell and an adult stem cell? We will build the conceptual framework and establish basic vocabulary that will be used throughout the course. DRB Stem Cells 2016 Hochedlinger.pdf

Review Article: Wu_and_Hochedlinger.pdf Yamanaka_timeline_2016_nrm.pdf

Lecture pdf's: 9-1-2017 lecture.pdf

Friday September 21, 2018 • Simches 3.120

I. Paper discussion: Pluripotency YangYang_et_al.pdf - Michael Mazzola

II. Lecture:

The stem cell Niche• Jay Rajagopal

Cells exhibit remarkable plasticity in terms of their ability to convert into other cell types. Mature functioning cells can dedifferentiate or transdifferentiate following injury to repair or maintain organ function. How is plasticity regulated and how does it contribute to organismal survival and tissue regeneration?

Review Article: Cellular plasticity- 1712 to the present day.pdf

Additional Review: NicheReview1.pdf

Friday September 28, 2018 • Simches 3.120

I. Paper discussion: Henna Hundal / Gurbani Kaur - The Stem Cell Niche: Pardo-Saganta.pdf

II. Lecture:

Heart development and regeneration • Burns

How are cardiac stem cells are specified, expanded, and differentiated during embryonic development? How can we augment the activity of either endogenous or transplanted cardiac stem cells for clinical use? Using the zebrafish as a model, we are identifying cardiac stem cell pools within the developing heart and dissecting their induction using both genetic and chemical-based screening strategies. Ultimately we assess the developmental potential of transplanted stem cells in disease models to investigate their regenerative capacity.

Review Article: npjregenmed201612.pdf

Friday October 5, 2018 • Simches 3.120

I. Paper discussion: Gurbani Kaur - Heart Regeneration Mohamed_Cell2018.pdf

II. Lecture:

Hematopoietic stem cells • Camargo

Hematopoietic stem cells (HSCs) are a major model for adult stem cell biology. This lecture will highlight novel technologies for lineage tracing HSCs and some unexpected results relating to hematopoietic cell differentiation.

Review Article: nature25022.pdf

Friday October 12, 2018 • Simches 3.120

I. Paper discussion: Michael Mazzola - Hematopoietic stem cells Clonal dynamics of native hematopoiesis.pdf

II. Lecture:

Neural stem cells, circuit plasticity and behavior • Sahay

Although the maturation of the mammalian brain is marked by the progressive restriction of cellular and neural plasticity, it is now known that the hippocampus is host to neurogenesis, the generation of functional neurons from neural stem cells, throughout life. What are the regulatory mechanisms that control adult hippocampal neurogenesis? Which molecular programs define the properties and connectivity of new neurons? Can stem cells and adult-born neurons influence learning and emotional behavior?

Review Article: Ming and Song Perspective 2011-1.pdf

Friday October 19, 2018 • Simches 3.120

I. Paper discussion: Aase Langan - Neural stem cells: Braun Ascl1 Sox10 NPC Oligo reprogramming 2015.pdf

II. Lecture:

Tendons and Bone • Galloway

Tendons, ligaments and bones are major components of our musculoskeletal system. Many studies have focused on the use of mesenchymal stem cells (MSCs) as potential new therapies for injury to these tissues. This class will present our current knowledge of tendon and bone development and regeneration and the questions surrounding MSC biology. We will discuss the major topics in the field and experimental approaches to address them.

Review Article: Dyment_Galloway_Review.pdf

Friday October 26, 2018 • Simches 3.120

I. Paper discussion: Gurbani Kaur - Tendons and Bone: Young_tendon_progenitor.pdf Young_tendon_SupMat.pdf

II. Lecture:

Digit tip regeneration • Lehoczky

The murine digit tip exhibits remarkable regeneration properties. Upon amputation, the digit tip undergoes epimorphic regeneration, a process involving the proliferation and differentiation of a mass of progenitor cells, termed the blastema, which gives rise to all of the regenerate tissue except the skin. Which molecular pathways and genes are necessary for blastema formation? How is proliferation and patterning coordinated to produce a properly formed digit? The potential for digit tip regeneration to model human limb regeneration will be discussed.

Review Article: seifert and muneoka review 2018.pdf

Friday November 2, 2018 • Simches 3.120

I. Paper discussion: Henna Handal - Digit tip regeneration Simkin Development 2017.pdf

II. Lecture:

Skin stem cells • Hsu

How are growth and differentiation controlled and coordinated to maintain tissue function during development, regeneration, and repair? The skin protects us from injury and dehydration, and facilitates sensory perception and thermoregulation. Throughout life the epidermis and its appendages renew themselves during homeostasis and heal themselves upon injury, requiring multiple reservoirs of stem cells. How does tissue growth homeostasis occur to meet physiological demands? How do stem cells communicate with niche cells to facilitate adaptation, and how does dysregulated stem cell behaviors lead to disease?

Review Article: Hsu_review.pdf

Friday November 9, 2018 • Simches 3.120

I. Paper discussion: Henna Hundal - Skin stem cells Agudo-Immunity-2018.pdf

II. Lecture:

Lineage and cell heterogeneity in tumors • Suva

How do the concepts of cell lineage, self-renewal, and stem cells apply to disease? How has the concept of cell lineage and tissue evolution changed how we think about cancer? Concepts of distinct tumor cell populations and lineages explored using single cell RNA seq illuminate heterogeneous properties of tumors.

Review Article: regev_nature21350.pdf

Friday November 16, 2018 • Pre-Proposal Outline Due

Optional early feedback on your research proposal aims and structure. A guideline for proposal structure can be found here: proposal outline.docx

Friday November 16, 2018 • Simches 3.120

I. Paper discussion: Aase Langan - Cancer heterogeneity and stem cells nature20123 no ED.pdf H3K27M scRNA-seq.pdf

II. Lecture:

Modeling neurological disease in a dish • Haggerty

Patient-specific, induced pluripotent stem cells (iPSCs) allow the generation of neuronal cell-based models that recapitulate key aspects of human neurological disease. How do we choose in vitro phenotypes that are the most relevant to disease pathophysiology? How can we use iPS cell models to investigate early events of disease pathogenesis?

Review Article: Haggarty.Neuropsych.iPSC.Review.2016.pdf

Friday November 30, 2018 • Research Proposal Due

An example of a successful proposal can be found here: CB226 example proposal.pdf

Friday November 30, 2018 • Simches 3.120

I. Paper discussion: Aase Langan - Modeling Neurological disease Haggarty.Pitt-Hopkins.Mol.Neuropsy.2017.pdf

II. Lecture:

Epithelial organ growth • Bardeesy

How do organs regenerate after injury and maintain size regulation? Epithelial regeneration will be discussed with regard to the concepts of adult stem cells vs regrowth of tissue from existing epithelial cells.

Review Article: annurev-physiol-021113-170255.pdf

Friday December 7, 2018 • Simches 3.120

I. Class Summary Discussion and Review

II. Lecture: Precision Medicine and Neurological disorders • Rubin

What is the best approach to finding cures for complex diseases? iPS cell screening approaches offer the potential to develop targeted therapeutics for stratified patient populations.

Cell Stem Cell Forum article: Gibbs Rubin.pdf