Lecture 2 - Early embryo development, pluripotency and lineage specification

Question 1

Define Stem cells

Answer 1

Stem cells are cells with the capacity to generate more specialised cell types, they give rise to specialised cells through differentiation
Live in a niche

Question 2

What are Progenitors (transit amplifying cellls) ?

Answer 2

Cells that proliferate for a limited number of cycles before differentiation are called progenitor cells

Question 3

What does self-renewl of Stem cells allow ?

Answer 3

It allows them to proliferate and maintain an undifferentiated state over an extended period of time. Self-renewal is critical for the long-term maintenance of stem cell populations and for their ability to generate multiple cell types during development and tissue regeneration.

Question 4

Define cell lineage

Answer 4

The developmental history of a differentiated cell as traced back to the cell from which it arises.

Question 5

Define Blastomere

Answer 5

The cell type of the early embryo that is generated by cleavage of the zygote

Question 6

Define Blastocyst

Answer 6

The spherical embryo at the time of implantation. The blastocyst consists of the primary tissue types: trophectoderm, epiblast and the primitive endoderm.

At blastocyst stage we lose potency and cells become pluripotent

Question 7

Define Trophectoderm

Answer 7

The precursor of the placenta

Question 8

Define Epiblast

Answer 8

the founding tissue of the embryo proper that gives rise to all fetal tissues

Question 9

Define Primitive endoderm

Answer 9

Extraembryonic tissue that initially covers the epiblast surface and later gives rise to the yolk sac tissue

Question 10

What are pluripotent cells ?

Answer 10

The ability of a cell to develop into all embryonic (but not extraembryonic) cell types including the germ cells

Question 11

Why do we use mice for studying embryos ?

Answer 11

The have short embryonic development and are also mammals like us.

Question 12

What is Totipotency ?

Answer 12

The ability of a cell to give rise to a fully functional organism (both embryonic and extraembryonic tissues)

Question 12

How does the totipotent blastomere develop ?

Answer 12

Totipotent blastomere -> Trophectoderm (TE) OR Inner cel mass (ICM)

TE gives rise to ectoderm

Inner cell mass -> Epiblast (EPI) OR Primitive endoderm (PrE)

Question 13

What is a hallmark of pluripotency?

Answer 13

Expression of pluripotent transcription factors (descriptive)
Found in ICM. Nanog, Oct4 and SOX2

Tetratocarcinoma formation (functional) (A TUMOUR WITH ALL CELL TYPES) - if pluripotent cells give rise to this during an assay this shows the cells are pluripotent. (KIDNEY)

Question 14

Define germ layers

Answer 14

the first specialised precursors of different embryonic cell types

Question 15

What is Gastrulation ?

Answer 15

embryo transforms from a 1D layer of epithelial cells (blastula) and reorganizes into a 3 layered structure gastrula.

Gastrulation occurs after implantation.

Question 16

What is included in the Germ layer Ectoderm ?

Answer 16

Surface, neural, neural crest
e.g. skin, peripheral and central NS

Question 17

What is included in the Germ layer Mesoderm ?

Answer 17

Axial, Paraxial, Intermediate, Lateral
e.g. Blood, heart, muscle, kidney

Question 18

What is included in the Germ layer Endoderm ?

Answer 18

Gut, Internal organs
e.g.liver, prancreas, intestine

Question 19

What is the primitive streak

Answer 19

It is a transient structure on the surface of the embryo as a groove and marks the beginning of gastrulation.
Appears when the anterior and posterior appear
It rises under the influence of signalling pathways WNT, BMP and FGF and Nodal. They regulate the fate and differentiation within the embryo
When it is blocked anterior grows

Question 20

Define Epithelium

Answer 20

These are cells that line the surface of a structure, characterized by tight cell junctions and polarized morphology.

Question 21

What is the Epithelial-to-mesenchyme transition?

Answer 21

A process during which cells lose their epithelial characteristics, gain a less regular appearance and become migratory.

Question 22

How do cells grow/ move during cell lineage specification ?

Answer 22

1. Epiblast cell movement towards the posterior/primitive streak
2. Breakdown of basement membrane
3. Loosening of cell-cell contacts
4. Cell migration

Early cell lineage specification occurs in a regionalised manner (ie the location of a cell predicts its identity) under the influence of sets of signals/genes/movements

Question 23

What are Neuromesodermal progenitors ?

Answer 23

NMPs are bipotent. As embryo elongates NMP undergoes self-renewal.
Give rise to either the spinal cord or paraxial mesoderm

NMPs arise posteriorly in the embryo

WNT and FGF signalling elevated in the NMP niche

Question 24

What is the descriptive gene marker for NMPs and its cells ?

Answer 24

NMPs T+SOX2+
Paraxial mesdoderm T+SOX2-
Spinal cord T-SOX2+

T and SOX2 are co-expressed, they differentiate into both mesodermal and neural lineages. This distinguishes them from other stem cell populations.

Question 25

What do defects in NMP specification lead to ?

Answer 25

Developmental abnormalities e.g spina bifida, Currarino syndrome, sacral agenesis, Spondylocostal dysostosis

Lack of mesoderm muscles are truncated

Question 26

What are neural stem cells ?

Answer 26

NSCs are found in the CNS (brain and spinal cord).
They are bipotent and have a self-renewal niche controlled by EGF and FGF. (SOX2+, RC2+ TFs)
They also differentiate into Glia (e.g. microglia/astrocytes/oligodendrocytes GFAP+) and neurones (TUJ1+)

Question 27

What are Haematopoietic stem cells ?

Answer 27

HSCs give rise to all blood cell types, they arise during development. They are multipotent. They arise in AGM. After birth their niche is in the bone marrow.

Question 28

What is the Aorta-gonad-mesonephros region ?

Answer 28

An embryonic tissue originating from the para-aortic splanchnopleura (P-Sp) and consisting of the dorsal aorta and urogenital ridges (UGR). It is involved in generating HSCs prior to the onset of hematopoiesis in the fetal liver.

HSCs can reconstitute the entire Haematopoietic system.

Question 29

What are the Transcription factors T and SOX

Answer 29

T (brachyury,) is a transcription factor for the formation of mesoderm during embryonic development. SOX2 a transcription factor that is involved in the maintenance of pluripotency in stem cells.

Question 30

What does the Inner cell mass give rise to?

Answer 30

Primitive endoderm and epiblast

Question 31

What is potency?

Answer 31

Ability of a cell to differentiate